11/3 - Systemic Disease Control - Oncology

Alkylating

What type of agents used in systemic cancer therapy attack DNA through bifunctional or monofunctional alkylation? Many of them are given orally, though the route does not predict the possible toxicity. Many of these agents have side effects which can be severe and life-threatening or irreversible, even if given properly. The most common agents in vet med include cyclophosphamide, chlorambucil, melphalan, and lomustine/CCNU.

Myelosuppression

What side effect is the most common result of alkylating agent administration?

Cyclophosphamide

Which alkylating agent is metabolized to its active form in the liver and can form sterile hemorrhagic cystitis?

Lomustine

Which alkylating agent is also called CCNU and crosses the blood-brain barrier? It can have a delayed nadir of 7-14 days and can cause hepatotoxicity.

Chlorambucil

Which alkylating agent, along with melphalan, can cause myelofibrosis with long-term use?

Platinum

Agents containing which heavy metal can be used for systemic cancer therapy, as the Cl groups bind to two sites on DNA? It can form intra or interstrand cross-links. These include cisplatin (IV, acute emesis, nephrotoxicity, ototoxicity, neurotoxicity, fatal pulmonary edema in cats) and carboplatin (IV, minimal nephrotoxicity, late nadir of 10-14 days, myelosuppression, and is safe in cats and does not require saline diuresis).

Antimetabolites

Which systemic cancer treatment agents have structures similar to the compounds required for synthesis of purines, pyrimidines, and nucleic acid? These are incorporated into DNA strands or block essential enzymes. They interfere with DNA synthesis and can be S phase specific. 5-fluorouracil is indicated for carcinoma and can cause neurotoxicity. Rabacfosidine/tanovea is indicated for lymphoma in dogs and can cause pulmonary fibrosis and dermatopathies. Cytosine arabinoside is indicated for renal/CNS lymphoma and has a short half life, and also crosses the BBB.

Antibiotics

Antitumor what drugs cause DNA damage by free radical formation and interference with topoisomerase II? This causes breaks or unwinding of DNA/RNA transcription.

Doxorubicin

Which antitumor antibiotic is also called adriamycin and is given IV? It is indicated for lymphoma, hemangiosarcoma, and carcinomas. It can cause cardiotoxicity in dogs, nephrotoxicity in cats, and mast cell degranulation/anaphylaxis. There can be orange urine, and the most common toxicity is GI.

Mitoxantrone

Which antitumor antibiotic is given IV and is a substitute for doxorubicin? This is given after cumulative doses of doxorubicin have already been reached. It causes blue/green urine and the most common toxicity is bone marrow.

Vinca

What type of alkaloids are mitotic inhibitors and inhibit formation of microtubules? They prevent microtubule assembly and can cause neurotoxicity, especially vincristine. Dose differences between drugs can cause improper administration.

L-asparaginase

What anti-tumor enzyme is derived from bacteria and degrades asparagine to deprive growing cells of this enzyme and inhibit protein synthesis? It can be given SC or IM and is indicated for LSA and acute lymphoblastic leukemia. Unique toxicities include hypersensitivity, anaphylaxis, and rarely pancreatitis. It is sparing to the BM and GI.

Cats

Therapeutic doses of cisplatin and 5-fluorouracil are both toxic to which animals?

Neutropenia

Both afebrile and febrile what blood cell condition can result from systemic cancer therapy? The afebrile form is treated by preventing fever formation, checking CBC at drug nadir, finding a neutrophil count under 1000 k/uL, treating with oral antibiotics and rechecking CBC after 5-7 days, and hospitalization if no improvement or reducing chemotherapy dose. The febrile form is seen with any degree of neutrophil decrease along with fever, which indicates sepsis. The bacteria usually originate in the gut and are usually sensitive to antibiotics. Treatment involves hospitalization, IV fluids and supportive care, resolution of fever, rechecking CBC in 5-7 days, and reducing chemotherapy dose.

MDR1

Mutations in what genes are found in breeds such as Australian shepherds, collies, long haired whippets, and shelties? This is important in chemotherapy as they will have increased GI toxicity and myelosuppression, active transportation of drugs by p-glycoprotein pump, and drugs like doxorubicin, vincristine, and vinblastine will have the strongest effects.

Toceranib

Which small molecule agent is also called Palladia and inhibits receptor tyrosine kinase and inhibits ATP? It is given orally and is indicated and FDA-approved for recurrent grade II and grade III MCTs. Extra-label use is for AGASACA or thyroid carcinoma. Toxicities include neutropenia, GI, and renal.

Verdinexor

Which small molecule agent is also called Laverdia-CA1 and inhibits chromosome region maintenance 1? Phase II clinical trials have been done for canine lymphoma and there is conditional approval for this purpose.

Tyrosinase

The oncept/melanoma vaccine protocol targets what enzyme? It has melanin differentiation antigens and is specific to the antigen. The goal is to break immune tolerance of the tumor. It is indicated in loco-regionally controlled oral malignant melanomas.